Inhibition of T cell homing by down-regulation of CD62L and the induction of a Th-2 response as a method to prevent acute allograft rejection in mice☆
| Autor: | Wulf Sienel, Anthony J. Slavin, Bernward Passlick, Christian Stremmel, S Eggeling |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Graft Rejection
Pulmonary and Respiratory Medicine Adoptive cell transfer T cell Down-Regulation Mice Inbred Strains Lymphocyte Activation Pertussis toxin Immune tolerance Mice Th2 Cells Immune system Cell Movement MHC class I Immune Tolerance Tumor Cells Cultured Animals Medicine L-Selectin Cells Cultured Interleukin 4 Cell Proliferation biology business.industry General Medicine Adoptive Transfer medicine.anatomical_structure Pertussis Toxin Acute Disease Immunology biology.protein Cytokines Female Surgery Cardiology and Cardiovascular Medicine business Neoplasm Transplantation Homing (hematopoietic) |
| Zdroj: | European Journal of Cardio-Thoracic Surgery. 30:362-369 |
| ISSN: | 1010-7940 |
| Popis: | For a successful immune response, migration of lymphocytes to lymphoid organs and other tissues is a key step, as the initial recognition of foreign antigens and activation of lymphocytes takes place in these organs. CD62L is a homing receptor that mediates entry of naïve T cells to peripheral lymph nodes. Maybe the preventing of T cell homing will change the immune response against allogeneic tissue and suppress rejection.We treated different mouse strains with pertussis toxin to manipulate T cell homing and measured the rejection of allografts in terms of allogeneic tumor cells. We transferred pertussis toxin treated or nontreated transgenic T cells into BALB/c wild type mice. The transgenic T cells could be followed ex vivo by specific antibodies. Cytokine production from purified (1x10(5)/ml) T cells after different stimulations in vitro and expression of surface markers on T cells following pertussis toxin treatment by FACS analysis were performed.Pertussis toxin-treated C57BL/6 mice with the MHC class I molecule H-2K(b) could not reject allogeneic tumor cells R1.1, which expressed the MHC class I molecule H-2K(k) and were killed by these cells. This allograft survival could be demonstrated for various allogeneic cells in different mouse strains with different MHC class I expression and emphasizes the general mechanism in these studies. In vivo CD62L expression on T cells was down-regulated by pertussis toxin in normal mice and transgenic mice that produce only one specific T cell, and after the pertussis toxin treatment the mice showed 4-5 times larger spleens compared to untreated mice. In transfer experiments, we demonstrated that CD62L low transgenic T cells could not home to lymph nodes. Furthermore, spleen cells from pertussis toxin-treated mice produced high amounts of the Th-2 cytokine interleukin 4 after stimulation in primary culture.Our data suggest that the inhibition of T cell homing changes the immune response. Prevention of homing of T cells in combination with the induction of a Th-2 response is a mechanism to prevent specific acute rejection of allogeneic tissue. |
| Databáze: | OpenAIRE |
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